Human Apoptosis-associated speck-like protein containing a CARD(PYCARD) ELISA kit

Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3. Involved in macrophage pyroptosis, a caspase-1-dependent inflammatory form of cell death and is the major constituent of the ASC pyroptosome which forms upon potassium depletion and rapidly recruits and activates caspase-1. In innate immune response believed to act as an integral adapter in the assembly of the inflammasome which activates caspase-1 leading to processing and secretion of proinflammatory cytokines. The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions. Required for recruitment of caspase-1 to inflammasomes containing certain pattern recognition receptors, such as NLRP2, NLRP3, AIM2 and probably IFI16. In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1. In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation. May be involved in DDX58-triggered proinflammatory responses and inflammasome activation. Isoform 2 may have a regulating effect on the function as inflammasome adapter. Isoform 3 seems to inhibit inflammasome-mediated maturation of interleukin-1 beta. In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8. In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form. Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways. For regulation of NF-kappa-B activating and inhibiting functions have been reported. Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK. Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing. Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA.

1. Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. PMID: 30279182
2. ASC specks as a putative biomarker of pyroptosis in myelodysplastic syndromes PMID: 30072146
3. results suggest that ASC, as a negative regulator of the MAVS-mediated innate immunity, may play an important role in host protection upon virus infection PMID: 29280086
4. PYCARD gene and its transcript variant may play a critical and regulative role in the inflflammatory response of primary gout patients with different phases and Chinese medicine syndromes. PMID: 29086221
5. ASC may be involved in tumor suppression and cell death via Bcl-2 and phosphor Src. PMID: 29459573
6. Data show that in HK-2 cells and unilateral nephrectomy model, ASC expression level is significantly augmented after treatment with contrast media. Its silencing attenuates contrast-induced apoptosis in HK-2 cell. PMID: 27721494
7. ASC specks released by microglia bind to amyloid-beta and increase amyloid-beta oligomer and aggregate formation, acting as an inflammation-driven cross-seed for amyloid-beta pathology PMID: 29293211
8. ASC contributes to oral cavity squamous cell carcinoma metastasis, and high-level ASC expression is a marker for poor prognosis in OSCC patients PMID: 27367024
9. ASC CpG methylation may prove to be a primary regulator of the pathogenesis of chronic inflammatory diseases such as heart failure. PMID: 26700661
10. besides its role in the inhibition of the NF-kappaB pathway, NLRC3 interferes with the assembly and activity of the NALP3 inflammasome complex by competing with ASC for pro-caspase-1 binding PMID: 28584053
11. ASC Induces Apoptosis via Activation of Caspase-9 by Enhancing Gap Junction-Mediated Intercellular Communication.( PMID: 28056049
12. These data revealed that cross-linking of ASC(PYD) filaments via ASC(CARD) mediates the assembly of ASC foci. PMID: 27069117
13. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. PMID: 28361856
14. loss of ASC driven tumor development is counterbalanced in the identical cell by the inhibition of pro-tumorigenic inflammation in the tumor cell itself PMID: 27768771
15. the deubiquitinating enzyme USP50 binds to the ASC protein and subsequently regulates the inflammasome signaling pathway. PMID: 28094437
16. ASC self-associates and binds NLRP3 PYD through equivalent protein regions, with higher binding affinity for the latter. These regions are located at opposite sides of the protein allowing multimeric complex formation previously shown in ASC PYD fibril assemblies. PMID: 27432880
17. Our data identify RIPK3 and the ASC inflammasome as key tumor suppressors in AML. PMID: 27411587
18. The role of the danger signals ASC and HMGB1 in the Fusobacterium nucleatum infection of gingival epithelial cells. PMID: 26687842
19. Data show that NOD-like receptor signaling genes NOD2, PYCARD, CARD6, and IFI16 are upregulated in psoriatic epidermis. PMID: 26976200
20. The methylated status of ASC/TMS1 promoter had the potential applicability for clinical evaluation the prognosis of gastric cancer PMID: 26260914
21. it appears that ASC transcript expression may be a surrogate marker for depression and may represent a link between depression and the altered immune responses observed in these categories of individuals with elevated depressive symptoms. PMID: 26750863
22. The proteins of NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells in cholesteatoma and chronic otitis media. PMID: 26457439
23. ASC/TMS1 methylation was significantly correlated with higher tumor nuclear grade. ASC/TMS1 is a novel functional tumor suppressor in renal carcinogenesis. PMID: 26093088
24. ASC Induces Procaspase-8 Death Effector Domain Filaments PMID: 26468282
25. ASC interacts with NALP3 and caspase-1 via different domains. PMID: 25567507
26. mRNA levels of Apoptosis-associated Speck-like protein were significantly higher in freshly isolated PBMCs from Chronic recurrent multifocal osteomyelitis patients in active disease than in healthy controls. PMID: 25061439
27. The proteins (HSP90b, TSM1 and L-plastin) in the current study may hold potential in differentiating between melanoma and benign nevi in diagnostically challenging cases. PMID: 25191796
28. caspase-1/ASC inflammasomes play a significant role in the activation of IL-1beta/ROS and NF-kappaB signaling of cytokine gene expression for T. cruzi control in human and mouse macrophages. PMID: 25372293
29. Neutralization of ASC improves sperm motility in men with spinal cord injuries. PMID: 25205754
30. Transcriptome analysis of human adipocytes implicates the NOD-like receptor pathway (NLRP3, PYCARD) in obesity-induced adipose inflammation. PMID: 25011057
31. Data indicate that apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is highly expressed in medulloblastomas. PMID: 24469054
32. R42W mutation had a significant effect on structure and increased stability. Although the R42W mutant exhibited reduced interaction with ASC PMID: 25006247
33. ASC PYD prevented complex formation with NALP3 PYD in vitro PMID: 24585381
34. Identify a novel innate immune signaling pathway (NLRP3-ASC-caspase-1-IL-1beta) activated by Ni(2+). PMID: 24158569
35. this study was to investigate the mRNA levels of AIM2 and ASC in a lymphocyte cell line (Jurkat) before and after MiR-143 introducing. PMID: 23811549
36. this study reports an interaction between promyelocytic leukemia protein and apoptosis-associated speck-like protein containing a caspase-activating recruitment domain (ASC). PMID: 24407287
37. PYCARD methylation is associated with colon cancer. PMID: 24169962
38. Activated AIM2 and NLRP3 nucleate PYD filaments of ASC, which, in turn, cluster the CARD of ASC. ASC thus nucleates CARD filaments of caspase-1, leading to proximity-induced activation.studies revealed a universal assembly process for ASC-dependent inflammasomes in both ALR and NLR families that involves nucleation-induced polymerization. PMID: 24630722
39. Study shows that T. gondii-induced IL-1beta production is dependent on the classical inflammasome components caspase-1 and ASC.Additionally, a role for a specific parasite factor, dense granule protein GRA15, in T. gondii induction of IL-1beta was demonstrated. PMID: 23839215
40. Reactivation of ASC protein expression in LS174T cells promotes sodium butyrate induced apoptosis. PMID: 23064206
41. The findings of this work may suggest a crucial relationship between mutant MEFV/pyrin and remarkable ASC up-regulation in familial Mediterranean fever inflammation. PMID: 22934972
42. These findings suggest stage-dependent dual roles of ASC in melanoma tumorigenesis. PMID: 22931929
43. central role of CARDs in the formation of ASC signalling platforms PMID: 23110696
44. ASC PYD can simultaneously self-associate and interact with NLRP3, rationalizing the model whereby ASC self-association upon recruitment to NLRP3 promotes clustering and activation of procaspase-1. PMID: 23066025
45. ASC in different tissues may influence tumor growth in opposite directions. PMID: 23090995
46. The study conclude that the frequency of TMS1/ASC gene methylation in cervical cancer is rare and have no any critical role in development of cervical cancer. PMID: 19258216
47. Gene expression profiles of ASC or CatB deficient human DCs show marked overlap with downregulation of genes implicated in DC function. PMID: 22732093
48. the requirement of TLR2/MyD88/NF-kappaB pathway (first signal) and ROS/potassium efflux (second signal) for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1beta release during RSV infection PMID: 22295065
49. Hypermethylation of ASC is associated with cholangiocarcinoma. PMID: 22230750
50. Caspase-1 protein induces apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-mediated necrosis independently of its catalytic activity. PMID: 21832064

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Cytoplasm. Inflammasome. Endoplasmic reticulum. Mitochondrion. Nucleus.; Golgi apparatus membrane.

Widely expressed at low levels. Detected in peripheral blood leukocytes, lung, small intestine, spleen, thymus, colon and at lower levels in placenta, liver and kidney. Very low expression in skeletal muscle, heart and brain. Expressed in lung epithelial

HGNC: 16608

OMIM: 606838

KEGG: hsa:29108

STRING: 9606.ENSP00000247470

UniGene: Hs.499094